He said: "The purpose of the review was to look at the case with fresh eyes and there is always real benefit in doing so. The review has further identified both investigative and forensic opportunities to support the Portuguese.

"There is more than a handful of people of interest which could be explored further if only to be eliminated.

"The key things are to investigate the case and our work is happening to support the Portuguese."

Madeleine, then nearly four, disappeared from her family's holiday apartment in Praia da Luz in Portugal's Algarve on May 3 2007, as her parents dined at a tapas restaurant with friends nearby.

As they marked the sixth anniversary of her disappearance earlier this month, her parents Kate and Gerry McCann said they remained hopeful as ever as Operation Grange continued, and that police seemed "more determined than ever".

"In many ways things haven't changed and you could argue that, with the Met review two years in, we are actually in a better place because so much more information has been collated and lots of pieces of the jigsaw have been filled," said Mr McCann.

The couple's hope was further reinforced by the recent discovery of Amanda Berry, Gina DeJesus and Michelle Knight in Ohio, a decade after they went missing in separate incidents.

When the women were found, the McCanns said the rescue of the women "reaffirmed" their hope of finding their daughter, which had never diminished.

"Their recovery is also further evidence that children are sometimes abducted and kept for long periods," they said in a statement.

"So we ask the public to remain vigilant in the ongoing search for Madeleine."

Mrs McCann, who recently returned to Portugal, said their family, including twins Sean and Amelie, now eight, had found a "new normality" since Madeleine's disappearance.

She encouraged anybody with any information to contact police, added: "'I think to encourage everybody, it's six years on, but the way the Met review is going is really positive and with that, new hope.